健康：肥満に関する記憶は細胞に書き込まれる

Fat tissue retains a ‘memory’ of obesity through cellular transcriptional and epigenetic changes that persist after weight loss, which might increase the chance of regaining weight, experiments in mouse and human cells show. The findings, published in Nature, may help to explain the problematic ‘yo-yo’ effect often seen with dieting or other weight loss strategies where individuals regain the lost weight and might inform future weight management strategies.

A primary goal in treating obesity and improving health is to reduce body weight to prevent secondary complications, such as type 2 diabetes or fatty liver disease. Strategies focusing on diet and lifestyle changes often result only in short-term weight loss, which may be regained over time — the yo-yo effect. This issue seems to be driven by a memory of obesity, but the mechanisms that underlie this effect are unclear.

Ferdinand von Meyenn and colleagues show that cells from human and mouse adipose tissue displayed transcriptional changes that are retained after appreciable weight loss. They identify these changes by comparing RNA sequences of cells within the fat tissue from 18 individuals without obesity with those from 20 individuals living with obesity before and after weight loss (at least a 25% reduction in BMI) following bariatric surgery. Similar analyses were carried out in lean, obese and formerly obese mice (the latter were obese then lost weight). In mice, they also found epigenetic changes (changes to the way that DNA is copied into RNA, which regulates gene expression) next to transcriptional changes which appear to be associated with impairments to some metabolic processes that persist after weight loss (such as fatty acid biosynthesis and the formation of fat cells), which may contribute to rebound weight gain after dieting, the authors suggest. Targeting these changes in fat and potentially other cells in the future could improve long-term weight management and health outcomes, the authors conclude.